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Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCA hospital-3M  = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA 3M-12M  = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (β DMN  = 0.85, p = 0.03; β SN  = 1.48, p < 0.01; β DAN  = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: Patients undergoing invasive coronary angiography (ICA) experience anxiety due to various reasons. Procedural anxiety can lead to physiological and psychological complications, compromising patient comfort and overall procedural outcomes. Benzodiazepines are commonly used to reduce periprocedural anxiety, although the effect is modest. Virtual reality (VR) is a promising non-pharmacological intervention to reduce anxiety in patients undergoing ICA., Methods and Analysis: A single-centre open-label randomised controlled trial is conducted assessing the effectiveness of add-on VR therapy on anxiety in 100 patients undergoing ICA and experiencing anxiety in a periprocedural setting. The primary outcome is the Numeric Rating Scale (NRS) anxiety score measured just before obtaining arterial access. Secondary outcomes include postarterial puncture and postprocedural anxiety, patient-reported outcome measures (PROMs) of anxiety and physiological measurements associated with anxiety. The NRS anxiety level and physiological measurements are assessed five times during the procedure. The PROM State-Trait Anxiety Inventory and Perceived Stress Scale are completed preprocedure, and the PROM STAI and the Igroup Presence Questionnaire are performed postprocedure., Ethics and Dissemination: The protocol of this study has been approved by the Research Ethics Committee of the Radboud University Medical Centre, the Netherlands (CMO Arnhem-Nijmegen, 2023-16586). Informed consent is obtained from all patients. The trial is conducted according to the principles of the Helsinki Declaration and in accordance with Dutch guidelines, regulations, and acts (Medical Research involving Human Subjects Act, WMO)., Registration Details: Trial registration number: NCT06215456., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Invasive haemodynamic monitoring of heart failure (HF) is used to detect deterioration in an early phase thereby preventing hospitalizations. However, this invasive approach is costly and presently lacks widespread accessibility. Hence, there is a pressing need to identify an alternative non-invasive method that is reliable and more readily available. In this pilot study, we investigated the relation between wrist-derived photoplethysmography (PPG) signals and the invasively measured pulmonary capillary wedge pressure (PCWP)., Methods and Results: Fourteen patients with aortic valve stenosis who underwent transcatheter aortic valve replacement with concomitant right heart catheterization and PPG measurements were included. Six unique features of the PPG signals [heart rate, heart rate variability, systolic amplitude (SA), diastolic amplitude, crest time (CT), and large artery stiffness index (LASI)] were extracted. These features were used to estimate the continuous PCWP values and the categorized PCWP (low < 12 mmHg vs. high ≥ 12 mmHg). All PPG features resulted in regression models that showed low correlations with the invasively measured PCWP. Classification models resulted in higher performances: the model based on the SA and the model based on the LASI both resulted in an area under the curve (AUC) of 0.86 and the model based on the CT resulted in an AUC of 0.72., Conclusion: These results demonstrate the capability to non-invasively classify patients into clinically meaningful categories of PCWP using PPG signals from a wrist-worn wearable device. To enhance and fully explore its potential, the relationship between PPG and PCWP should be further investigated in a larger cohort of HF patients., Competing Interests: Conflict of interest: N.T.B.S. none; A.E.v.R. none; R.E. none; A.J.M.v.d.E. none. N.M.D.A.v.M. received institutional research grant support outside the scope of the submitted work from Abbott, Teleflex, Astra Zenica, PulseCath BV, Pie Medical, Boston Scientific, Daiichi-Sankyo, Edward Lifesciences, Medtronic, Biotronik, and CSI; J.J.B. received independent research grant from Abbott to the institute for ISS and has had speaker engagement or advisory boards in the past 5 years with Astra Zeneca, Abbott, Boehringer-Ingelheim, Bayer, Daiichi Sankyo, Novartis, and Vifor; J.L.B. none; N.B. none. R.M.A.v.d.B. received an independent research grant to the institute from Abbott and has had speaker engagement or advisory boards in the past 5 years with Abbott, Boehringer Ingelheim, and Bayer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests., Methods: In this prospective multicentre study in three university medical centres in the Netherlands, adult patients (aged 18 years or older) in whom short-lasting circulatory arrest was induced as part of routine practice (transcatheter aortic valve implantation, defibrillation testing, or ventricular tachycardia induction) were eligible for inclusion. Exclusion criteria were a known bilateral significant subclavian artery stenosis or medical issues interfering with the wearing of the wristband. After providing informed consent, patients were equipped with a photoplethysmography wristband during the procedure. Invasive arterial blood pressure and electrocardiography were continuously monitored as the reference standard. Development of the photoplethysmography algorithm was based on three consecutive training cohorts. For each cohort, patients were consecutively enrolled. When a total of 50 patients with at least one event of circulatory arrest were enrolled, that cohort was closed. Validation was performed on the fourth set of included patients. The primary outcome was sensitivity for the detection of circulatory arrest., Findings: Of 306 patients enrolled between March 14, 2022, and April 21, 2023, 291 patients were included in the data analysis. In the development phase (n=205), the first training set yielded a sensitivity for circulatory arrest detection of 100% (95% CI 94-100) and four false positive alarms; the second training set yielded a sensitivity of 100% (94-100), with six false positive alarms; and the third training set yielded a sensitivity of 100% (94-100), with two false positive alarms. In the validation phase (n=86), the sensitivity for circulatory arrest detection was 98% (92-100) and 11 false positive circulatory arrest alarms. The positive predictive value was 90% (95% CI 82-94)., Interpretation: The automated detection of induced circulatory arrests using wrist-derived photoplethysmography is feasible with good sensitivity and low false positives. These promising findings warrant further development of this wearable technology to enable automated cardiac arrest detection and alarming in a home setting., Funding: Dutch Heart Foundation (Hartstichting)., Competing Interests: Declaration of interests KE is a data scientist at Corsano Health. RJB received a research grant from Biosense Webster, and payment for a lecture from The Cardiovascular Education Institute. KV received a research grant from Medtronic; consulting fees from Medtronic, Abbott, and Biosense Webster; a speakers fee from Philips; participates in the advisory board of Medtronic; and received educational grants from Medtronic, Abbott, and Biosense Webster. S-CY is a consultant of Boston Scientific; has received research grants from Biotronik, Medtronic, and Boston Scientific; received personal payments for presentations from Boston Scientific, Biotronik, and Medtronic; and his institution received payment for his participation on a Data Safety Monitoring Board from Boston Scientific. ER received consulting fees from Corsano Health. NvM received grants from Abbott Vascular, Boston Scientific, Medtronic, Edwards Lifesciences, Daiichi Sankyo, and AstraZeneca; received personal consulting fees from Abbott Vascular, Boston Scientific, Medtronic, Anteris, JenaValve, Daiichi Sankyo, AstraZeneca, Amgen, Siemens, and Pie Medical; and received payment for presentations from Abbott Vascular, Biotronik, Amgen, Daiichi Sankyo, Medtronic, and Boston Scientifc. PCS is the CEO of Corsano Health. NvR received a research grant from the Dutch Heart Foundation related to this manuscript; received research grants from Biotronik, Abbott, Medtronic, and Philips, not related to this manuscript; and speaker fees were received from Abbott, Bayer, RainMed, and Microport, not related to this manuscript. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Out-of-hospital cardiac arrest (OHCA) is a major healthcare problem, with approximately 200 weekly cases in the Netherlands. Its critical, time-dependent nature makes it a unique medical situation, of which outcomes strongly rely on infrastructural factors and on-scene care by emergency medical services (EMS). Survival to hospital discharge is poor, although it has substantially improved, to roughly 25% over the last years. Recognised key factors, such as bystander resuscitation and automated external defibrillator use at the scene, have been markedly optimised with the introduction of technological innovations. In an era with ubiquitous smartphone use, the Dutch digital text message alert platform HartslagNu ( www.hartslagnu.nl ) increasingly contributes to timely care for OHCA victims. Guidelines emphasise the role of cardiac arrest recognition and early high-quality bystander resuscitation, which calls for education and improved registration at HartslagNu. As for EMS care, new technological developments with future potential are the selective use of mechanical chest compression devices and extracorporeal life support. As a future innovation, 'smart' defibrillators are under investigation, guiding resuscitative interventions based on ventricular fibrillation waveform characteristics. Taken together, optimisation of available prehospital technologies is crucial to further improve OHCA outcomes, with particular focus on more available trained volunteers in the first phase and additional research on advanced EMS care in the second phase., (© 2021. The Author(s).)

Importance: Increased bystander cardiopulmonary resuscitation (CPR) is essential to improve survival after cardiac arrest. Although most studies focus on technical CPR skills, the randomized Lowlands Saves Lives trial prespecified a follow-up survey on other important aspects that affect the widespread performance of CPR., Objective: To investigate bystander willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness 6 months after undergoing short face-to-face and virtual reality (VR) CPR trainings., Design, Setting, and Participants: A prespecified 6-month posttraining survey was conducted among 320 participants in the Lowlands Saves Lives trial, a randomized comparison between 20-minute face-to-face, instructor-led CPR training and VR training. Participants were recruited at the Lowlands music festival, with a designated area to conduct scientific projects (August 16-18, 2019; the Netherlands). Statistical analysis was performed from March 1, 2020, to July 31, 2021., Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training using CPR manikins or VR training using the Resuscitation Council (UK)-endorsed Lifesaver VR smartphone application and a pillow to practice compressions., Main Outcomes and Measures: Primary outcomes were willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness as reported by the entire cohort. As secondary analyses, the results of the 2 training modalities were compared., Results: Of 381 participants, 320 consented to this follow-up survey; 188 participants (115 women [61%]; median age, 26 years [IQR, 22-32 years]) completed the entire survey and were accordingly included in the secondary analysis. The overall proportion of participants willing to perform CPR on a stranger was 77% (144 of 188): 81% (79 of 97) among face-to-face participants and 71% (65 of 91) among VR participants (P = .02); 103 participants (55%) reported feeling scared to perform CPR (P = .91). Regarding theoretical knowledge retention, a median of 7 (IQR, 6-8) of 9 questions were answered correctly in both groups (P = .81). Regarding dissemination of CPR awareness, 65% of participants (123 of 188) told at least 1 to 10 family members or friends about the importance of CPR, and 15% (29 of 188) had participated in certified, instructor-led training at the time of the survey, without differences between groups., Conclusions and Relevance: In this 6-month posttraining survey, young adult participants of short CPR training modules reported high willingness (77%) to perform CPR on a stranger, with slightly higher rates for face-to-face than for VR participants. Theoretical knowledge retention was good, and the high dissemination of awareness suggests that these novel CPR training modules staged at a public event are promising sensitizers for involvement in CPR, although further challenges include mitigating the fear of performing CPR., Trial Registration: ClinicalTrials.gov Identifier: NCT04013633.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P =0.86). Generalized linear model: (β, 0.991; 95% CI, 0.894-1.099; P =0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P <0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Introduction: In cardiac arrest, ventricular fibrillation (VF) waveform characteristics such as amplitude spectrum area (AMSA) are studied to identify an underlying myocardial infarction (MI). Observational studies report lower AMSA-values in patients with than without underlying MI. Moreover, experimental studies with 12-lead ECG-recordings show lowest VF-characteristics when the MI-localisation matches the ECG-recording direction. However, out-of-hospital cardiac arrest (OHCA)-studies with defibrillator-derived VF-recordings are lacking., Methods: Multi-centre (Amsterdam/Nijmegen, the Netherlands) cohort-study on the association between AMSA, ST-elevation MI (STEMI) and its localisation. AMSA was calculated from defibrillator pad-ECG recordings (proxy for lead II, inferior vantage point); STEMI-localisation was determined using ECG/angiography/autopsy findings., Results: We studied AMSA-values in 754 OHCA-patients. There were statistically significant differences between no STEMI, anterior STEMI and inferior STEMI (Nijmegen: no STEMI 13.0mVHz [7.9-18.6], anterior STEMI 7.5mVHz [5.6-13.8], inferior STEMI 7.5mVHz [5.4-11.8], p = 0.006. Amsterdam: 11.7mVHz [5.0-21.9], 9.6mVHz [4.6-17.2], and 6.9mVHz [3.2-16.0], respectively, p = 0.001). Univariate analyses showed significantly lower AMSA-values in inferior STEMI vs. no STEMI; there was no significant difference between anterior and no STEMI. After correction for confounders, adjusted absolute AMSA-values were numerically lowest for inferior STEMI in both cohorts, and the relative differences in AMSA between inferior and no STEMI was 1.4-1.7 times larger than between anterior and no STEMI., Conclusion: This multi-centre VF-waveform OHCA-study showed significantly lower AMSA in case of underlying STEMI, with a more pronounced difference for inferior than for anterior STEMI. Confirmative studies on the impact of STEMI-localisation on the VF-waveform are warranted, and might contribute to earlier diagnosis of STEMI during VF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Shock-resistant ventricular fibrillation (VF) poses a therapeutic challenge during out-of-hospital cardiac arrest (OHCA). For these patients, new treatment strategies are under active investigation, yet underlying trigger(s) and substrate(s) have been poorly characterised, and evidence on coronary angiography (CAG) data is often limited to studies without a control group., Methods: In our OHCA-registry, we studied CAG-findings in OHCA-patients with VF who underwent CAG after hospital arrival. We compared baseline demographics, arrest characteristics, CAG-findings and outcomes between patients with VF that was shock-resistant (defined as >3 shocks) or not shock-resistant (≤3 shocks)., Results: Baseline demographics, arrest location, bystander resuscitation and AED-use did not differ between 105 patients with and 196 patients without shock-resistant VF. Shock-resistant VF-patients required more shocks, with higher proportions endotracheal intubation, mechanical CPR, amiodaron and epinephrine. In both groups, significant coronary artery disease (≥1 stenosis >70%) was highly prevalent (78% vs. 77%, p = 0.76). Acute coronary occlusions (ACOs) were more prevalent in shock-resistant VF-patients (41% vs. 26%, p = 0.006). Chronic total occlusions did not differ between groups (29% vs. 33%, p = 0.47). There was an association between increasing numbers of shocks and a higher likelihood of ACO. Shock-resistant VF-patients had lower proportions 24-h survival (75% vs. 93%, p < 0.001) and survival to discharge (61% vs. 78%, p = 0.002)., Conclusion: In this cohort of OHCA-patients with VF and CAG after transport, acute coronary occlusions were more prevalent in patients with shock-resistant VF compared to VF that was not shock-resistant, and their clinical outcome was worse. Confirmative studies are warranted for this potentially reversible therapeutic target., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: In cardiac arrest, ventricular fibrillation (VF) waveform analysis has identified the amplitude spectrum area (AMSA) as a key predictor of defibrillation success and favorable neurologic survival. New resuscitation protocols are under investigation, where prompt defibrillation is restricted to cases with a high AMSA. Appreciating the variability of in-field pad placement, we aimed to assess the impact of recording direction on AMSA-values, and the inherent defibrillation advice., Methods: Prospective VF-waveform study on 12-lead surface electrocardiograms (ECGs) obtained during defibrillation testing in ICD-recipients (2010-2017). AMSA-values (mVHz) of simultaneous VF-recordings were calculated and compared between all limb leads, with lead II as reference (proxy for in-field pad position). AMSA-differences between leads I and II were quantified using Bland-Altman analysis. Moreover, we investigated differences between these adjacent leads regarding classification into high (≥15.5), intermediate (6.5-15.5) or low (≤6.5) AMSA-values., Results: In this cohort (n = 243), AMSA-values in lead II (10.2 ± 4.8) differed significantly from the other limb leads (I: 8.0 ± 3.4; III: 12.9 ± 5.6, both p < 0.001). The AMSA-value in lead I was, on average, 2.24 ± 4.3 lower than in lead II. Of the subjects with high AMSA-values in lead II, only 15% were classified as high if based on assessments of lead I. For intermediate and low AMSA-values, concordances were 66% and 72% respectively., Conclusions: ECG-recording direction markedly affects the result of VF-waveform analysis, with 20-30% lower AMSA-values in lead I than in lead II. Our data suggest that electrode positioning may significantly impact shock guidance by 'smart defibrillators', especially affecting the advice for prompt defibrillation., (© 2021 The Authors.)

Background Dissemination of cardiopulmonary resuscitation (CPR) skills is essential for cardiac arrest survival. Virtual reality (VR)-training methods are low cost and easily available, but to meet depth requirements adaptations are required, as confirmed in a recent randomized study on currently prevailing CPR quality criteria. Recently, the promising clinical performance of new CPR quality criteria was demonstrated, based on the optimal combination of compression depth and rate. We now study compliance with these newly proposed CPR quality criteria. Methods and Results Post hoc analysis of a randomized trial compared standardized 20-minute face-to-face CPR training with VR training using the Lifesaver VR smartphone application. During a posttraining test, compression depth and rate were measured using CPR mannequins. We assessed compliance with the newly proposed CPR criteria, that is, compression rate within ±20% of 107/minute and depth within ±20% of 47 mm. We studied 352 participants, age 26 (22-31) years, 56% female, and 15% with CPR training ≤2 years. Among VR-trained participants, there was a statistically significant difference between the proportions complying with newly proposed versus the currently prevailing quality criteria (52% versus 23%, P <0.001). The difference in proportions complying with rate requirements was statistically significant (96% for the new versus 50% for current criteria, P <0.001), whereas there was no significant difference with regard to the depth requirements (55% versus 51%, P =0.45). Conclusions Lifesaver VR training, although previously found to be inferior to face-to-face training, may lead to CPR quality compliant with recently proposed, new quality criteria. If the prognostic importance of these new criteria is confirmed in additional studies, Lifesaver VR in its current form would be an easily available vector to disseminate CPR skills.

Background In cardiac arrest, computerized analysis of the ventricular fibrillation (VF) waveform provides prognostic information, while its diagnostic potential is subject of study. Animal studies suggest that VF morphology is affected by prior myocardial infarction (MI), and even more by acute MI. This experimental in-human study reports on the discriminative value of VF waveform analysis to identify a prior MI. Outcomes may provide support for in-field studies on acute MI. Methods and Results We conducted a prospective registry of implantable cardioverter defibrillator recipients with defibrillation testing (2010-2014). From 12-lead surface ECG VF recordings, we calculated 10 VF waveform characteristics. First, we studied detection of prior MI with lead II, using one key VF characteristic (amplitude spectrum area [AMSA]). Subsequently, we constructed diagnostic machine learning models: model A, lead II, all VF characteristics; model B, 12-lead, AMSA only; and model C, 12-lead, all VF characteristics. Prior MI was present in 58% (119/206) of patients. The approach using the AMSA of lead II demonstrated a C-statistic of 0.61 (95% CI, 0.54-0.68). Model A performance was not significantly better: 0.66 (95% CI, 0.59-0.73), P =0.09 versus AMSA lead II. Model B yielded a higher C-statistic: 0.75 (95% CI, 0.68-0.81), P <0.001 versus AMSA lead II. Model C did not improve this further: 0.74 (95% CI, 0.67-0.80), P =0.66 versus model B. Conclusions This proof-of-concept study provides the first in-human evidence that MI detection seems feasible using VF waveform analysis. Information from multiple ECG leads rather than from multiple VF characteristics may improve diagnostic accuracy. These results require additional experimental studies and may serve as pilot data for in-field smart defibrillator studies, to try and identify acute MI in the earliest stages of cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) is a major cause of death. Although the aetiology of cardiac arrest can be diverse, the most common cause is ischaemic heart disease. Coronary angiography and percutaneous coronary intervention, if indicated, has been associated with improved long-term survival for patients with initial shockable rhythm. However, in patients without ST-segment elevation on the post-resuscitation electrocardiogram, the optimal timing of performing this invasive procedure is uncertain. One important challenge that clinicians face is to appropriately select patients that will benefit from immediate coronary angiography, yet avoid unnecessary delay of intensive care support and targeted temperature management. Observational studies have reported contradictory results and until recently, randomised trials were lacking. The Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) was the first randomised trial that provided comparative information between coronary angiography treatment strategies. This literature review will provide the current knowledge and gaps in the literature regarding optimal care for patients successfully resuscitated from OHCA in the absence of ST-segment elevation and will primarily focus on the role and timing of coronary angiography in this high-risk patient population.

Importance: Bystander cardiopulmonary resuscitation (CPR) is crucial for survival after cardiac arrest but not performed in most cases. New, low-cost, and easily accessible training methods, such as virtual reality (VR), may reach broader target populations, but data on achieved CPR skills are lacking., Objective: To compare CPR quality between VR and face-to-face CPR training., Design, Setting, and Participants: Randomized noninferiority trial with a prospective randomized open blinded end point design. Participants were adult attendees from the science section of the Lowlands Music Festival (August 16 to 18, 2019) in the Netherlands. Analysis began September 2019., Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training or VR training using a smartphone app endorsed by the Resuscitation Council (United Kingdom)., Main Outcomes and Measures: During a standardized CPR scenario following the training, we assessed the primary outcome CPR quality, measured as chest compression depth and rate using CPR manikins. Overall CPR performance was assessed by examiners, blinded for study groups, using a European Resuscitation Council-endorsed checklist (maximum score, 13). Additional secondary outcomes were chest compression fraction, proportions of participants with mean depth (50 mm-60 mm) or rate (100 min-1-120 min-1) within guideline ranges, and proportions compressions with full release., Results: A total of 381 participants were randomized: 216 women (57%); median (interquartile range [IQR]) age, 26 (22-31) years. The VR app (n = 190 [49.9%]) was inferior to face-to-face training (n = 191 [50.1%]) for chest compression depth (mean [SD], VR: 49 [10] mm vs face to face: 57 [5] mm; mean [95% CI] difference, -8 [-9 to -6] mm), and noninferior for chest compression rate (mean [SD]: VR: 114 [12] min-1 vs face to face: 109 [12] min-1; mean [95% CI] difference, 6 [3 to 8] min-1). The VR group had lower overall CPR performance scores (median [IQR], 10 [8-12] vs 12 [12-13]; P < .001). Chest compression fraction (median [IQR], 61% [52%-66%] vs 67% [62%-71%]; P < .001) and proportions of participants fulfilling depth (51% [n = 89] vs 75% [n = 133], P < .001) and rate (50% [n = 87] vs 63% [n = 111], P = .01) requirements were also lower in the VR group. The proportion of compressions with full release was higher in the VR group (median [IQR], 98% [59%-100%] vs 88% [55%-99%]; P = .002)., Conclusions and Relevance: In this randomized noninferiority trial, VR training resulted in comparable chest compression rate but inferior compression depth compared with face-to-face training. Given the potential of VR training to reach a larger target population, further development is needed to achieve the compression depth and overall CPR skills acquired by face-to-face training., Trial Registration: ClinicalTrials.gov identifier: NCT04013633.

Aim: To minimize termination of resuscitation (TOR) in potential survivors, the desired positive predictive value (PPV) for mortality and specificity of universal TOR-rules are ≥99%. In lack of a quantitative summary of the collective evidence, we performed a diagnostic meta-analysis to provide an overall estimate of the performance of the basic and advanced life support (BLS and ALS) termination rules., Data Sources: We searched PubMed/EMBASE/Web-of-Science/CINAHL and Cochrane (until September 2019) for studies on either or both TOR-rules in non-traumatic, adult cardiac arrest. PRISMA-DTA-guidelines were followed., Results: There were 19 studies: 16 reported on the BLS-rule (205.073 patients, TOR-advice in 57%), 11 on the ALS-rule (161.850 patients, TOR-advice in 24%). Pooled specificities were 0.95 (0.89-0.98) and 0.98 (0.95-1.00) respectively, with a PPV of 0.99 (0.99-1.00) and 1.00 (0.99-1.00). Specificities were significantly lower in non-Western than Western regions: 0.84 (0.73-0.92) vs. 0.99 (0.97-0.99), p < 0.001 for the BLS rule. For the ALS-rule, specificities were 0.94 (0.87-0.97) vs. 1.00 (0.99-1.00), p < 0.001. For non-Western regions, 16 (BLS) or 6 (ALS) out of 100 potential survivors met the TOR-criteria. Meta-regression demonstrated decreasing performance in settings with lower rates of in-field shocks., Conclusions: Despite an overall high PPV, this meta-analysis highlights a clinically important variation in diagnostic performance of the BLS and ALS TOR-rules. Lower specificity and PPV were seen in non-Western regions, and populations with lower rates of in-field defibrillation. Improved insight in the varying diagnostic performance is highly needed, and local validation of the rules is warranted to prevent in-field termination of potential survivors., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Updates of resuscitation guidelines have limited high-level supporting evidence. Moreover, the overall effect of such bundled practice changes depends not only on the impact of the individual interventions but also on their interplay and swift functioning of the entire chain of survival. Therefore, real-world data monitoring is essential. We performed a meta-analysis of comparative studies on outcomes before and after successive guideline updates. On January 16, 2019, we searched for comparative studies (PubMed, Web-of-Science, Embase, and the Cochrane Libraries) reporting outcomes before and after resuscitation guidelines 2005, 2010, and 2015. We followed PRISMA, Cochrane, and Moose-recommendations. Studies on outcomes during the 2005 versus 2000 guideline period (n = 23; 40,859 patients) reported significantly higher ROSC (odds ratio [OR] 1.21 [1.04 to 1.42], p = 0.014), survival to admission (OR 1.34 [1.09 to 1.65], p = 0.005), survival to discharge (OR 1.46 [1.25 to 1.70], p <0.001), and favorable neurologic outcome (OR 1.35 [1.01 to 1.81], p = 0.040). Studies on outcomes during the 2010 versus 2005 guideline period (n = 11; 1,048,112 patients) indicated no difference in ROSC (OR 1.25 [95% confidence interval 0.95 to 1.63], p = 0.11), whereas survival to discharge improved significantly (OR 1.30 [1.17 to 1.45], p <0.001). Only 2 studies reported on neurologic outcomes, both showing improved outcome after the 2010 guideline update. No data on the 2015 guidelines were available. This meta-analysis on real-world data of >1 million patients demonstrates improved outcomes after the 2005 and 2010 resuscitation guideline updates, and a lack of data on the 2015 guideline. In conclusion, although limited in terms of causality, this study suggests that the sum of all efforts to improve outcomes, including updated CPR guidelines, contributed to increased survival after cardiac arrest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Layperson cardiopulmonary resuscitation (CPR) is a key aspect in the chain of survival after cardiac arrest. New, low-cost, easily accessible training methods such as virtual reality (VR) training with a smartphone application may reach broader populations, but data on CPR performance are scarce., Methods and Analysis: The Lowlands Saves Lives trial is a prospective randomised open-blinded end-point evaluation study, comparing two 20 min CPR training protocols: standardised, certified instructor-led face-to-face training complying with current education guidelines (using Laerdal Little Anne manikins), and VR training, using the UK Resuscitation Council endorsed Lifesaver VR app. In the latter, chest compressions are practiced on a pillow.During VR training, participants learn to resuscitate by completing a filmed CPR scenario while wearing VR goggles and headphones. Eligible for inclusion are adult attendees of Lowlands Science, a specific section of the 3-day Lowlands music festival (50 000 attendees), dedicated exclusively to science. Following the training, all participants will perform a CPR test on a Laerdal Resusci Anne QCPR manikin. Primary outcome measures are depth and rate of chest compressions, measured using CPR manikins. The key secondary outcome is overall CPR performance, with real-time examination (blinded for study group) of all items of a European Resuscitation Council endorsed checklist, and evaluation of a sample of videotaped CPR tests by a blinded event committee.Given the unique setting of a festival, the primary additional analysis will address the impact of alcohol levels on CPR quality parameters and overall performance. Follow-up questionnaires will evaluate the attitude towards performing CPR. This unique study may provide important insights into innovative CPR training methods, factors that impact CPR performance and the impact on long-term attitude towards resuscitation., Ethics and Dissemination: This study received approval from the research ethics committee of the Radboudumc. All participants will provide written informed consent. The results of this study will be published in peer-reviewed journals and presented at (inter)national conferences., Trial Registration Number: ClinicalTrials.gov registry (NCT04013633)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The amplitude spectrum area (AMSA) of the ventricular fibrillation (VF) waveform predicts shock success and clinical outcome after out-of-hospital cardiac arrest (OHCA). Recently, also AMSA-changes demonstrated prognostic value. Until now, most studies focused on early shocks, while many patients require prolonged resuscitations. We studied AMSA and its changes in relation to shock success, for both the early and later phase of resuscitation., Methods: Per-shock VF-waveform analysis of a prospective OHCA-cohort (Nijmegen, The Netherlands). The absolute AMSA and relative AMSA-changes (ΔAMSA) were calculated from three-second VF-segments prior to defibrillation. Shocks were categorised as early (#1-3) or late (#4-8). Shock success was defined as return of organised rhythm., Results: Shock success was 46% for early (131/286) and 52% for late shocks (85/162), p = 0.18. Early shock success varied from 23% to 70% with increasing quartiles of AMSA (p-trend<0.001). For late shocks, there also was an association with AMSA, with a narrower range in shock success from 43% to 68% (p-trend = 0.04). Higher values of ΔAMSA were associated with shock success in the early, but not in the later phase., Conclusion: AMSA relates to shock success during the entire resuscitation, but associations were most apparent for early shocks. AMSA-changes were also associated with shock success, but only in the early phase of resuscitation. In an era of smart defibrillators, absolute AMSA and relative changes hold promise for studies on early guidance of resuscitation, whereas additional studies are warranted to further characterize shock prediction in the later phase., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Out-of-hospital cardiac arrests (OHCAs) are a major healthcare problem. Over the years, several initiatives have contributed to more lay volunteers providing cardiopulmonary resuscitation (CPR) and increased use of automated external defibrillators (AEDs) in the Netherlands. As part of a quality and outcomes program, we registered bystander CPR, AED use and outcome in the Nijmegen area., Methods: Prospective resuscitation registry with a study cohort of non-traumatic OHCA cases from 2013-2016 and historical controls from 2008-2011. In line with previous reports, we studied patients transported to the hospital (Radboudumc, Nijmegen, the Netherlands) and excluded arrests witnessed by the emergency medical service (EMS). Primary outcomes were return of spontaneous circulation (ROSC) and survival to discharge., Results: In the study cohort (n = 349) the AED was attached more often than in the historical cohort (n = 180): 46% vs. 23% and the proportion of bystander CPR was higher: 78% vs. 63% (both p < 0.001). A higher proportion of patients received an AED shock (39% vs. 15%, p < 0.001) and the number of required shocks by the EMS was lower (2 vs. 4, p = 0.004). Survival to discharge was higher (47% vs. 33%, p = 0.002) without differences in ROSC. The survival benefit was restricted to patients with a shockable initial rhythm. In both cohorts, bystander CPR and AED use were independently associated with survival., Conclusion: In patients admitted after OHCA, survival to discharge has markedly improved to 40-50%, comparable with other Dutch registries. As increased bystander CPR and the doubled use of AEDs seem to have contributed, all civilian-based resuscitation initiatives should be encouraged.

Background: Despite a promising association between VF waveform characteristics and prognosis after resuscitation, studies with VF-guided treatment have so far not improved outcomes. While driven by the idea that the VF waveform reflects arrest duration, increasing evidence suggests that pre-existent disease-related changes of the myocardium affect ECG-characteristics of VF as well. In this context, we studied the impact of the left ventricular (LV) diameter and mass., Methods: Cohort of 193 ICD-patients with defibrillation testing at the Radboudumc (2010-2014). Surface ECG-recordings (leads I,II,aVF,V1,V3,V6) were analysed to study amplitude and frequency characteristics of the induced VF. Both for LV diameter and mass, patients were categorised in two groups, using echocardiographic data (ASE-guidelines)., Results: In all ECG-leads, dominant and median frequencies were significantly lower in patients with (n=40) than in patients without (n=151) an increased LV diameter. The mean amplitude and amplitude spectrum area (AMSA) did not differ. In contrast, we observed no differences in frequency characteristics in relation to the LV mass, whereas mean amplitude (I,aVF,V3) and AMSA (I,V3) were significantly higher in patients with (n=57) than in patients without (n=120) an increased LV mass., Conclusions: Frequency characteristics of VF were consistently lower in case of an increased LV diameter. Whereas LV mass does not affect the frequency of the VF waveform, amplitudes seem higher with increasing mass. These findings add to the current knowledge of factors that modulate VF characteristics of the surface ECG and provide insight into factors which may be accounted for in future studies on VF-guided resuscitative interventions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology., Methods and Results: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82])., Conclusion: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing., (© 2016 Wiley Periodicals, Inc.)

Background: Of the proposed algorithms that provide guidance for in-field termination of resuscitation (TOR) decisions, the guidelines for cardiopulmonary resuscitation (CPR) refer to the basic and advanced life support (ALS)-TOR rules. To assess the potential consequences of implementation of the ALS-TOR rule, we performed a case-by-case evaluation of our in-field termination decisions and assessed the corresponding recommendations of the ALS-TOR rule., Methods: Cohort of non-traumatic out-of-hospital cardiac arrest (OHCA)-patients who were resuscitated by the ALS-practising emergency medical service (EMS) in the Nijmegen area (2008-2011). The ALS-TOR rule recommends termination in case all following criteria are met: unwitnessed arrest, no bystander CPR, no shock delivery, no return of spontaneous circulation (ROSC)., Results: Of the 598 cases reviewed, resuscitative efforts were terminated in the field in 46% and 15% survived to discharge. The ALS-TOR rule would have recommended in-field termination in only 6% of patients, due to high percentages of witnessed arrests (73%) and bystander CPR (54%). In current practice, absence of ROSC was the most important determinant of termination [aOR 35.6 (95% CI 18.3-69.3)]. Weaker associations were found for: unwitnessed and non-public arrests, non-shockable initial rhythms and longer EMS-response times., Conclusion: While designed to optimise hospital transportations, application of the ALS-TOR rule would almost double our hospital transportation rate to over 90% of OHCA-cases due to the favourable arrest circumstances in our region. Prior to implementation of the ALS-TOR rule, local evaluation of the potential consequences for the efficiency of triage is to be recommended and initiatives to improve field-triage for ALS-based EMS-systems are eagerly awaited., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Study Objective: Mechanical chest compression devices have been developed to facilitate continuous delivery of high-quality cardiopulmonary resuscitation (CPR). Despite promising hemodynamic data, evidence on clinical outcomes remains inconclusive. With the completion of 3 randomized controlled trials, we conduct a meta-analysis on the effect of in-field mechanical versus manual CPR on clinical outcomes after out-of-hospital cardiac arrest., Methods: With a systematic search (PubMed, Web of Science, EMBASE, and the Cochrane Libraries), we identified all eligible studies (randomized controlled trials and nonrandomized studies) that compared a CPR strategy including an automated mechanical chest compression device with a strategy of manual CPR only. Outcome variables were survival to hospital admission, survival to discharge, and favorable neurologic outcome., Results: Twenty studies (n=21,363) were analyzed: 5 randomized controlled trials and 15 nonrandomized studies, pooled separately. For survival to admission, the pooled estimate of the randomized controlled trials did not indicate a difference (odds ratio 0.94; 95% confidence interval 0.84 to 1.05; P=.24) between mechanical and manual CPR. In contrast, meta-analysis of nonrandomized studies demonstrated a benefit in favor of mechanical CPR (odds ratio 1.42; 95% confidence interval 1.21 to 1.67; P<.001). No interaction was found between the endorsed CPR guidelines (2000 versus 2005) and the CPR strategy (P=.27). Survival to discharge and neurologic outcome did not differ between strategies., Conclusion: Although there are lower-quality, observational data that suggest that mechanical CPR used at the rescuer's discretion could improve survival to hospital admission, the cumulative high-quality randomized evidence does not support a routine strategy of mechanical CPR to improve survival or neurologic outcome. These findings are irrespective of the endorsed CPR guidelines during the study periods., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Characteristics of the ventricular fibrillation (VF) waveform reflect arrest duration and have been incorporated in studies on algorithms to guide resuscitative interventions. Findings in animals indicate that VF characteristics are also affected by the presence of a previous myocardial infarction (MI). As studies in humans are scarce, we assessed the impact of a previous MI on VF characteristics in ICD-patients., Methods: Prospective cohort of ICD-patients (n=190) with defibrillation testing at the Radboudumc (2010-2013). VF characteristics of the 12-lead surface ECG were compared between three groups: patients without a history of MI (n=88), with a previous anterior (n=47) and a previous inferior MI (n=55)., Results: As compared to each of the other groups, the mean amplitude and amplitude spectrum area were lower, for an anterior MI in lead V3 and for an inferior MI in leads II and aVF. Across the three groups, the bandwidth was broader in the leads corresponding with the infarct localisation. In contrast, the dominant and median frequencies only differed between previous anterior MI and no history of MI, being lower in the former., Conclusions: The VF waveform is affected by the presence of a previous MI. Amplitude-related measures were lower and VF was less organised in the ECG-lead(s) adjacent to the area of infarction. Although VF characteristics of the surface ECG have so far primarily been considered a proxy for arrest duration and metabolic state, our findings question this paradigm and may provide additional insights into the future potential of VF-guided resuscitative interventions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Ventricular fibrillation (VF) waveform characteristics are associated with cardiac arrest duration and defibrillation success. Recent animal studies found that VF characteristics and shock success also depend on the presence of myocardial infarction (MI). In patients, VF induction after implantable cardioverter defibrillator (ICD) implantation offers a unique setting to study early VF characteristics: we studied the relation with cardiac disease--either presence or absence of a previous MI--and with shock success., Methods: Retrospective cohort study of ICD-patients who underwent defibrillation testing, 117 (63%) with and 69 (37%) without a previous MI. Intracardiac recordings of induced VF were analysed using Fourier analysis., Results: In previous MI-patients, the fundamental frequency and organisation index of the VF signal were significantly lower as compared with patients without a previous MI: 4.9 Hz ± 0.6 vs. 5.2 Hz ± 0.6 (p = 0.005) and 56% ± 10 vs. 60% ± 9 (p = 0.001), respectively. The median frequency was not different (p = 0.25). We found no association between VF characteristics and ICD shock success., Conclusions: In analogy with observations in animals, we found that a history of a previous MI was associated with slower and less organised VF. In our cohort of ICD-patients, early VF waveform characteristics were not associated with shock outcomes. Further study is warranted to determine to what extent VF characteristics are influenced by the underlying aetiology on the one hand, and time delay on the other. These findings could improve insight into the potential value of VF analysis to guide shock delivery., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)